Observational Study of the Long-term Effect of Latanoprost in Normal Tension Glaucoma

Mean horizontal cup to disc (cup/disc or C/D) ratio measured by slit lamp examination to assess progression of glaucoma; calculated as the ratio of the diameter of the depression (cup) to that of the optical nerve head (disc). Valid range: 0.1-1.0. Only data for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: PP; N = number of participants with horizontal cup to disc ratio data at baseline and at least 1 post-baseline visit; change analyzed for participants with a non-missing response at baseline and observation. Last Visit: change in participants with a non-missing response at both baseline and at least one post-baseline visit.

Mean vertical cup to disc (cup/disc or C/D) ratio measured by slit lamp examination to assess progression of glaucoma; calculated as the ratio of the diameter of the depression (cup) to that of the optical nerve head (disc). Valid range: 0.1-1.0; a high cup/disc ratio may imply glaucoma. Only data for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: PP. N = number of participants with vertical cup to disc ratio at baseline and at least 1 post-baseline visit; change analyzed for participants with a non-missing response at baseline and observation. Last Visit: change in vertical cup to disc ratio in participants with a non-missing response at both baseline and at least one post-baseline visit.

Mean retinal nerve fiber layer (RNFL) thickness in millimeters (mm) right and left eye assessed by HRT imaging. Valid range: 0.100 to 0.400 mm. Only the RNFL for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: PP; n = number of participants with a non-missing response at both visits (baseline and observation). Last Visit = last post-baseline visit at which participant provides a value for RNFL thickness.

Rim area (millimeter \[mm\]2) right and left eye assessed by HRT imaging. Valid range: 0.500 to 1.900 mm2. Only the rim area for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: PP; n = number of participants with a non-missing response at both visits (baseline and observation). Last Visit = last post-baseline visit at which participant provides a value for rim area.

Rim volume (mm3) right and left eye assessed by HRT imaging. Valid range: 0.080 to 0.700 mm3. Only the rim volume for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: PP; n = number of participants with a non-missing response at both visits (baseline and observation). Last Visit = last post-baseline visit at which participant provides a value for rim volume.

Cup shape measure right and left eye assessed by HRT imaging . Valid range: -0.400 to -0.010. Only the cup shape measure for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: PP; n = number of participants with a non-missing response at both visits (baseline and observation). Last Visit = last post-baseline visit at which participant provides a value for cup shape measure.

Mean IOP values measured by applanation tonometry or noncontact method; valid range: 8-40 millimeters of mercury (mmHg). Only the IOP reading for the eye treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed. Last visit = last post-baseline visit at which participant provides a value of IOP.

Time frame: Baseline, Month 6, Month 12, Month 18, Month 24, Last Visit

Population: Per protocol (PP) analysis set: all participants in the Full Analysis Set (at least 1 dose of Xalatan® and 1 post-baseline IOP measurement) who were treated for ≥18 months; had at least BL and 1 post-BL non-missing efficacy assessments for IOP at least 18 months apart; without ametropy at BL; and without additional glaucoma medication during study.

Response: Yes = had IOP 24-hour pressure peak; No = did not have IOP 24-hour pressure peak.

Time frame: Month 12

Population: PP; N = number of participants with analyzable data at observation. The total number of participants by visit with an IOP peak response of 'Yes' differs from those with numerical values of IOP peaks since 1 of the 2 fields was populated for certain participants.

Response: Yes = had IOP 24-hour pressure peak; No = did not have IOP 24-hour pressure peak.

Time frame: Month 24

Population: PP; N = number of participants with analyzable data at observation. The total number of participants by visit with an IOP peak response of 'Yes' differs from those with numerical values of IOP peaks since 1 of the 2 fields was populated for certain participants.

Response: Yes = had an IOP 24-hour profile; No = did not have an IOP 24-hour profile.

Time frame: Month 12

Population: PP; N = number of participants with analyzable data at observation.

Response: Yes = had an IOP 24-hour profile; No = did not have an IOP 24-hour profile.

Time frame: Month 24

Population: PP; N = number of participants with analyzable data at observation.

Values of change in Aulhorn Stage measured by Humphrey Visual Field Analyzer. Aulhorn stages: no scotoma, Stage I (relative scotomas only), Stage II (absolute scotomas without connection to blind spot), Stage III (absolute scotomas with connection to blind spot), Stage IV (absolute scotomas more than 1 quadrant affected), and Stage V (temporal residual visual field only). If both eyes were treated with Xalantan® the value of right eye was analyzed; otherwise, only the assessment for the eye treated with study medication was used.

Time frame: Baseline, Month 24

Population: PP; N = number of participants who provided Aulhorn stage values of 1 to 5 at both baseline and month 24 visits.

Change in mean defect right and left eye; valid range: -30 - + 30 decibels (dB). Visual field defect categories: preperimetric glaucoma: ≥ -2 dB; mild damage: \< -2 dB and ≥ -3.3 dB; moderate damage: \< -3.3 dB and ≥ -4.6 dB; and severe damage: \< -4.6 dB. If both eyes were treated with Xalatan® , the value for the right eye was used; otherwise, only the mean defect value for the eye treated with study medication was used.

Time frame: Baseline, Month 24

Population: PP; N = number of participants who provided a Mean Defect value at both Baseline and Month 24 visits.

Increase in Aulhorn Stage by at least one stage (last visit minus baseline). Three different visual field defect categories defined using Aulhorn stage values 1-5: Aulhorn stage 1 = mild damage, Aulhorn stages 2, 3 = moderate damage, Aulhorn stages 4, 5 =severe damage.

Time frame: Month 24 (or last visit)

Population: PP; results based on participants with a value for Aulhorn Stage at both Baseline and at least one post-baseline visit. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Increase in Horizontal Cup to Disc Ratio and/or Vertical Cup to Disc Ratio by at least 0.2 (Last Visit minus Baseline).

Time frame: Month 24 (or last visit)

Population: PP; results based on participants with both a Baseline and at least one post-baseline visit. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Decrease in mean defect by at least 2.5 decibels (dB) (Last Visit minus Baseline).

Time frame: Month 24 (or last visit)

Population: PP; results based on participants with a value for mean defect at both Baseline and at least one post-baseline visit. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Participants with at least one post-baseline optic disc hemorrhage.

Time frame: Month 24 (or last visit)

Population: PP; results based on participants with at least one post-baseline assessment of optic disc hemorrhage. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Decrease in at least one Heidelberg Retina Tomograph (HRT) parameter by: Rim Area 0.2 millimeter (mm)2, Rim Volume 0.1 mm3, or mean retinal nerve fiber layer (RNFL) Thickness 0.1 mm, (Last Visit minus Baseline).

Time frame: Month 24 (or last visit)

Population: PP; results based on participants with a value of the variable in question at both Baseline and at least one post-baseline visit. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Visual Field Deterioration rated as progressive by physician on at least one post-baseline visit; range: 1= improved 2= stable 3= progressive. If both eyes were treated with Xalatan® the value for the right eye was used; otherwise, only the assessment for the eye treated with study medication was used.

Time frame: Month 24 (or last visit)

Population: PP; results based on participants with at least one post-baseline assessment of change in visual field defect. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Number of participants with Investigator assessments of the efficacy of Xalatan® treatment rated as: 1=very good, 2=good, 3=moderate, 4=insufficient. If study medication was stopped before 24 months, assessment was performed at the time of early termination.

Time frame: Month 24

Population: PP; N = number of participants with a non-missing response at Month 24 visit.

Presence of optic disc hemorrhages assessed by slip lamp examination. Only data for eye were treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Month 12

Population: PP; N = number of participants who indicated whether or not they had an optic disc hemorrhage at the given visit.

Presence of optic disc hemorrhages assessed by slip lamp examination. Only data for eye were treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Month 18

Population: PP; N = number of participants who indicated whether or not they had an optic disc hemorrhage at the given visit.

Presence of optic disc hemorrhages assessed by slip lamp examination. Only data for eye were treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Month 24

Population: PP; N = number of participants who indicated whether or not they had an optic disc hemorrhage at the given visit.

Presence of optic disc hemorrhages assessed by slip lamp examination. Only data for eye were treated with Xalatan® was used; if both eyes were treated, the value of the right eye was analyzed.

Time frame: Month 6

Population: PP; N = number of participants who indicated whether or not they had an optic disc hemorrhage at the given visit.

Percentage of participants who achieved their IOP target set at baseline. Response: Yes = achieved IOP target at last vist; No = did not achieve IOP target at last visit.

Time frame: Month 24, (or last visit)

Population: PP; n = number of subjects in the Per Protocol Analysis Set with a non-missing response at Last Visit. Last visit = last post-baseline visit at which participant provides a value of IOP.

Overall progression defined as at least 1 of the 6 individual progression of glaucoma damage measures met: increase in horizontal cup to disc ratio and/or vertical cup to disc ratio by at least 0.2; at least 1 post Baseline (BL) optic-disc hemorrhage; decreased rim area (0.2 mm2), rim volume (0.1 mm3), mean retinal nerve fiber layer (RNFL)(0.1 mm), progressive visual field deterioration, increase in Aulhorn stage (by at least 1 stage), and/or decrease in mean defect by at least 2.5 decibels \[dB\])

Time frame: Month 24 (or last visit)

Population: PP; to be included in the percentage, participants must have provided a response for at least one of the six individual progression of glaucoma damage measures. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Progression (Last Visit minus Baseline) defined as increase in horizontal cup to disc ratio and/or vertical cup to disc ratio by at least 0.2, and/or decrease in at least 1 of Heidelberg Retina Tomograph (HRT) parameters (deterioration of rim area 0.2 mm2; deterioration of rim volume 0.1 mm3 deterioration or mean retinal nerve fiber layer (RNFL) thickness 0.1 mm).

Time frame: Month 24 (or last visit)

Population: PP; to be included in the percentage, participants must have provided a response for at least one of following events: increase in horizontal or vertical cup to disc ratio, or decrease in rim area, rim volume, or mean RNFL thickness. Last Visit = last post-baseline visit at which participant provides a value for the relevant outcome measure.

Progression defined as visual field deterioration rated progressive by physician on at least 1 post-baseline visit, and increase in Aulhorn stage (by at least 1 stage) and/or decrease in mean defect by at least 2.5 dB (Last Visit minus Baseline).

Time frame: Month 24 (or last visit)

Population: PP; to be included in the percentage, participants must have had Visual Field Deterioration rated as progressive by the physician on at least 1 post-baseline visit, and at least one measure of increase in Aulhorn Stage by at least 1 stage, and decrease in Mean Defect by at least 2 dB (last visit minus baseline).